title: Alport syndrome and leiomyomatosis: the first deletion extending beyond COL4A6 intron 2.
abstract: Alport syndrome (ATS) is a nephropathy characterized by the association of progressive hematuric nephritis with ultrastructural changes of the glomerular basement membrane (thinning, thickening, and splitting), sensorineural deafness, and variable ocular abnormalities (anterior lenticonus, macular flecks, and cataracts). The most common mode of transmission is X-linked inheritance, due to COL4A5 mutations. X-linked ATS is rarely associated with diffuse leiomyomatosis (DL), a benign hypertrophy of the visceral smooth muscle in gastrointestinal, respiratory, and female reproductive tracts. The ATS-DL complex is due to deletions that encompass the 5' ends of the COL4A5 and COL4A6 genes and include the bidirectional promoter. In this paper, we described 3 ATS-DL cases, 2 familial and 1 sporadic bearing a deletion encompassing the 5'-end of both the COL4A5 and COL4A6 genes, as identified by multiplex ligation-dependent probe amplification (MLPA) analysis. The array-CGH technique allowed a better definition of deletion size, confirming that the proximal breakpoint was within COL4A6 intron 2 in 2 cases. Surprisingly, 1 case had a deletion extending proximally beyond exon 3 of COL4A6, as confirmed by qPCR analysis. This is the largest deletion reported to date that has been associated with ATS-DL and this case should lead us to reconsider the mechanisms that might be involved in the development of diffuse leiomyomatosis.
authors.affiliation: Department Molecular Biology, Medical Genetics, University of Siena, V. Le Bracci 2, 53100, Siena, Italy.
authors.forename: Vera
authors.initials: V
authors.lastname: Uliana
authors.forename: Elena
authors.initials: E
authors.lastname: Marcocci
authors.forename: Mafalda
authors.initials: M
authors.lastname: Mucciolo
authors.forename: Ilaria
authors.initials: I
authors.lastname: Meloni
authors.forename: Claudia
authors.initials: C
authors.lastname: Izzi
authors.forename: Carlo
authors.initials: C
authors.lastname: Manno
authors.forename: Mirella
authors.initials: M
authors.lastname: Bruttini
authors.forename: Francesca
authors.initials: F
authors.lastname: Mari
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Alessandra
authors.initials: A
authors.lastname: Renieri
authors.forename: Leonardo
authors.initials: L
authors.lastname: Salviati
mesh_terms: D000328:Adult; D001483:Base Sequence / Q000235:genetics*; D002648:Child; D024141:Collagen Type IV / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics; D018231:Leiomyomatosis; D008297:Male; D008969:Molecular Sequence Data; D009394:Nephritis, Hereditary / Q000235:genetics; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics*; D055815:Young Adult
chemical_list: C478159:COL4A5 protein, human; C559044:COL4A6 protein, human; D024141:Collagen Type IV